PLK2
protein-codingpolo like kinase 2
Gene summary
The protein encoded by this gene is a member of the polo family of serine/threonine protein kinases that have a role in normal cell division. This gene is most abundantly expressed in testis, spleen and fetal tissues, and its expression is inducible by serum, suggesting that it may also play an important role in cells undergoing rapid cell division. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006622.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 42 | 1 | 43 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 0 | 48 | 1 | 1 | 51 |
Highest pathogenic variant AF is 0.0000018625581
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006613.2 | 14 | MANE Select | |
| Ensembl | ENSP00000274289.3 | 14 | MANE Select | |
| RefSeq | NP_001239155.1 | 15 | Standard | |
| Ensembl | ENSP00000478685.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| plk2b | Danio rerio | Structure: dorsal longitudinal anastomotic vessel Quality: aplastic/hypoplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- FoxO signaling pathway - Homo sapiens (human)
- Glucocorticoid Receptor Pathway
- Nuclear Receptors Meta-Pathway
- TP53 Regulates Transcription of Cell Cycle Genes
- Gene expression (Transcription)
Biological Process
- G1/S transition of mitotic cell cycle
- protein phosphorylation
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
- mitotic spindle organization
- mitotic cell cycle checkpoint
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- ATP-dependent protein binding
- protein-containing complex binding
Cellular Component
- chromatin
- cytoplasm
- centrosome
- centriole
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274289
- Coding exons
- 14
- Length
- 6279
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125725
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.01 | 207 | 370 | 0.559 | 0.0000178 | 4530 |
| Missense (PolyPhen) | 69 | 171.09 | 0.40329 | 2146 | ||
| Synonymous | -1.16 | 155 | 138 | 1.13 | 0.00000702 | 1270 |
| Loss of Function | 5.17 | 2 | 35.0 | 0.0571 | 0.00000175 | 425 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress. {ECO:0000269|PubMed:15242618, ECO:0000269|PubMed:19001868, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:20531387}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.0433
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |